Abstract: High alert medications have an increased potential to cause serious harm to patients if they are taken improperly, medication errors are a major cause of morbidity and mortality in health care system. Purpose: To examine the effect of traditional health education versus clinical supervision model on pediatric nurses' adherence to high alert medication safety. Design: A Quasi- experimental design was utilized. Sample: Convenient sample of 80 pediatric nurses. Setting: This study was conducted at post-natal and neonatal intensive care units in “Menoufia university hospital and Shebin el-kom teaching hospital". Instruments: Three instruments were used to collect data; Instrument one includes social characteristics of studied nurses. Instrument two, structured interview questionnaire sheets to assess nurses' knowledge about high alert medication safety. Instrument three, observational checklist for nurses' adherence to high alert medications safety. Results: Nurses who receive educational intervention based on a clinical supervision model have a higher level of adherence to high-alert medication safety (81.8%) than nurses who receive traditional health education (72%). There were highly statistically significant differences between nurses adherence in study group 2 and study group 1 on pre- and post-tests (P=0.001). Conclusion: Implementation of educational intervention guidelines based on clinical supervision model improved pediatric nurses' knowledge and adherence to high alert medication safety that could help to reduce medication error and decreased morbidity and mortality of children in ICUs. Recommendations: Continuous education programs should be designed and implemented for nurses about safe use of high alert medications to improve their knowledge and practice.